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Antidepressant Safety Debate May Include Adult Patients

The yearlong debate over whether antidepressant drugs increase the risk of suicide in some children may soon widen to include adults, as English and Canadian scientists are reporting findings from three new analyses of suicide risk in people over age 18 who have taken the medications.

The new findings are mixed, and apparently contradictory, and likely to encourage both patient advocates who believe that antidepressants like Prozac have hidden dangers, and manufacturers who insist that the medications are safe, experts said.

One of the reports, an analysis of data on antidepressants from previous studies, found that adults taking the drugs were twice as likely to attempt suicide as those receiving a dummy pill or other treatments, but no more likely to complete the act.

The two other reports found no significant link between the medications and suicide. Suicide attempts occurred in less than 0.5 percent of the more than 200,000 people included in the three studies.

All three papers appeared yesterday in the online version of The British Medical Journal.

"There has been a phenomenal amount of pressure to study this issue in adults," in part because of the debate over the risk in children, said Dr. John Geddes, a professor of epidemiological psychiatry at Oxford University and the co-author of an accompanying editorial in the journal. Dr. Geddes was not involved in the studies and has received research money from drug makers.

"We know a certain amount of negative evidence on these drugs has been suppressed, and the more information we have on them in the public domain, the better to guide clinical practice," he said.

In the early 1990's, a panel of experts convened by the Food and Drug Administration concluded that there was not enough evidence to link drugs like Prozac and Zoloft to increased suicide risk and most psychiatrists say that the drugs are more likely to prevent suicide.

But regulators in the United States and Britain recently issued warnings that the drugs, known as selective serotonin reuptake inhibitors, or S.S.R.I.'s, could raise the risk of suicidal thinking in a small number of children and adolescents. The F.D.A. is scrutinizing suicide attempts by adults reported in drug trials.

The risk is extremely difficult to determine, experts say, in part because suicide attempts are rare.

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In one of the new analyses, researchers at the University of Ottawa re-evaluated data from 345 antidepressant trials for depression and other conditions, involving 36,455 men and women. The investigators found 143 total suicide attempts, and found that the rate was twice as high in people who were taking S.S.R.I.'s as it was in those getting placebo pills, or some other form of therapy.

"Many people are on these drugs, which makes the rare risk very important," said Dr. Dean Fergusson of the University of Ottawa, who is a lead author of the study.

Dr. David A. Freedman, a clinical trials expert and statistician at the University of California, Berkeley, who was not involved in any of the studies, said that reviews of this kind are not a very reliable way to determine risks. Moreover, he said, the Ottawa study presumed that all antidepressants affected everyone the same way in terms of suicide risk.

"This is like saying your reaction to Prozac is the same as mine to Zoloft, which we know isn't true," he said. "This assumption exaggerates the significance of their findings."

Dr. Fergusson disagreed, saying the assumption of uniform effect gave a conservative estimate.

In another analysis, also in the British journal, doctors evaluated data from 477 trials involving 40,826 people, which were submitted by drug companies to British regulators for safety review. "We found no evidence that S.S.R.I.'s increased the risk of suicide," and weak evidence that the drugs increased the risk of self harm, the authors concluded.

The third study analyzed case records of 146,095 people prescribed antidepressants for the first time from 1995 to 2001. The researchers found no evidence of increased suicide risk in adults taking S.S.R.I.'s compared with people of the same age and similar histories taking other types of antidepressants.

Given that studies report suicidal behavior in a number of ways, experts are skeptical that reviews of trial data will resolve the issue. "We have machinery to pull diamonds from the earth, but we don't have machinery to pull truth from data in these studies," Dr. Freedman said.

Psychiatrists said the studies were not likely to change how they treat patients: the drugs tend to increase agitation and unusual behavior in the first few weeks after the treatment is started, when patients need to be closely monitored, they said.

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A version of this article appears in print on February 18, 2005, on Page A00017 of the National edition with the headline: Antidepressant Safety Debate May Include Adult Patients. Order Reprints|Today's Paper|Subscribe